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Updated: Jul 24, 2025
Bronchoalveolar Lavage Exosomes in Lipopolysaccharide-induced Septic Lung Injury
Published on: May 21, 2018
Small Extracellular Vesicles Secreted by iPSC-Derived MSCs Ameliorate Pulmonary Inflammation and Lung Injury Induced
Wei Peng1,2, Yun Yang3, Jiaquan Chen1,2
1Department of Critical Care Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
Background:
Sepsis-induced acute lung injury is a common critical illness in intensive care units with no effective treatment is currently available. Small extracellular vesicles, secreted by mesenchymal stem cells (MSCs), derived from human-induced pluripotent stem cells (iMSC-sEV), possess striking advantages when incorporated MSCs and iPSCs, which are considered extremely promising cell-free therapeutic agents. However, no studies have yet been conducted to systemically examine the effects and underlying mechanisms of iMSC-sEV application on attenuated lung injury under sepsis conditions.
Method:
iMSC-sEV were intraperitoneally administered in a rat septic lung injury model induced by cecal ligation and puncture (CLP). The efficacy of iMSC-sEV was assessed by histology, immunohistochemistry, and pro-inflammatory cytokines of bronchoalveolar lavage fluid. We also evaluated the in vitro effects of iMSC-sEV on the activation of the inflammatory response in alveolar macrophages (AMs). Small RNA sequencing was utilized to detect changes in the miRNA expression profile in lipopolysaccharide (LPS)-treated AMs after iMSC-sEV administration. The effects of miR-125b-5p on the function of AMs were studied.
Results:
iMSC-sEV were able to attenuate pulmonary inflammation and lung injury following CLP-induced lung injury. iMSC-sEV were internalized by AMs and alleviated the release of inflammatory factors by inactivating the NF-κB signaling pathway. Moreover, miR-125b-5p showed a fold-change in LPS-treated AMs after iMSC-sEV administration and was enriched in iMSC-sEV. Mechanistically, iMSC-sEV transmitted miR-125b-5p into LPS-treated AMs to target TRAF6.
Conclusion:
Our findings demonstrated that iMSC-sEV treatment protects against septic lung injury and exerts anti-inflammatory effects on AMs at least partially through miR-125b-5p, suggesting that iMSC-sEV may provide a novel cell-free strategy for the treatment of septic lung injury.
Insights
Human induced pluripotent stem cell-derived small extracellular vesicles (iMSC-sEV) show promise in treating sepsis-induced acute lung injury by reducing inflammation in lung cells. These vesicles deliver miR-125b-5p to macrophages, offering a potential cell-free therapeutic strategy.
Area of Science:
- Regenerative Medicine
- Cell Biology
- Immunology
Background:
- Sepsis-induced acute lung injury is a critical condition lacking effective treatments.
- Human induced pluripotent stem cell-derived small extracellular vesicles (iMSC-sEV) are promising cell-free therapeutics.
- The therapeutic effects and mechanisms of iMSC-sEV on septic lung injury remain underexplored.
Purpose of the Study:
- To investigate the therapeutic efficacy of iMSC-sEV in a rat model of septic lung injury.
- To elucidate the underlying mechanisms of iMSC-sEV in attenuating lung inflammation.
Main Methods:
- Septic lung injury was induced in rats using cecal ligation and puncture (CLP).
- iMSC-sEV treatment efficacy was assessed via histology and cytokine analysis.
- In vitro studies evaluated iMSC-sEV effects on alveolar macrophages (AMs) and miRNA profiles.
- The role of miR-125b-5p in iMSC-sEV mediated effects was investigated.
Main Results:
- iMSC-sEV administration attenuated pulmonary inflammation and lung injury in CLP-induced rats.
- iMSC-sEV were internalized by AMs, reducing inflammatory factor release via NF-κB pathway inhibition.
- miR-125b-5p was upregulated in AMs post-iMSC-sEV treatment and identified as a key mediator, targeting TRAF6.
Conclusions:
- iMSC-sEV treatment offers protection against septic lung injury.
- The anti-inflammatory effects on AMs are mediated, at least partially, by miR-125b-5p.
- iMSC-sEV represent a potential novel cell-free therapeutic strategy for septic lung injury.
